Detection, activation mechanism and its clinical application of basic fibroblast growth factor in renal cell carcinoma.

肾细胞癌中碱性成纤维细胞生长因子的检测、激活机制及其临床应用

• 批准号: 03670741
• 负责人: NONOMURA Katsuya
• 金额: $ 1.34万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670741/
• 关键词: Renal cell carcinoma; Basic fibroblast growth factor (bFGF); von Hippel-Lindau (VHL) disease; Collagenase activity; 塩基性線維芽細胞増殖因子(bFGF); von Hippel-Lindau(VHL)病; 細胞外コラ-ゲンマトリクス; 組織内コラ-ゲナ-ゼ活性

Von Hippel-Lindau (VHL) disease which is manifested by cerebellar hemangioblastomas, retinal angiomas and cysts of the pancreas,kidney and epididymis is well known to be highly associated with renal cell carcinoma (RCC). Sporadic RCC is also known to be one of highly vascularized tumors. These clinical evidence supposes us an intimate association between the growth and proliferation of RCC and tumor angiogenesis. Although endothelial cells of blood vessels generally have a very slow turnover time, basic fibroblast growth factor (bFGF) is said to stimulate the endothelial cells and to induce the formation of new capillaries which ultimately sustain the growth of a solid tumor.bFGF activity was assayed and compared among 12 specimens (10 were sporadic and 2 were with VHL disease) of RCC and their corresponding autologous normal renal tissue. bFGFs in sporadic RCC and normal renal tissue were 98.2*38.68 and 143.2*31.16 fmol/mg. protein (Mean*SD, n=10), respectively. bFGF activity in malignant tissue was significantly lower than that in the corresponding autologous normal tissue. Otherwise, bFGF activities of RCC and non-malignant renal tissue in 2 case with VHL disease were 137, 632 and 82, 44 fmol/mg. protein, respectively.In general, bFGF as an inert form exists in the extracellular matrix. The collagenase activity might have an important role in terms of disruption of the extracellular matrix and of mobilization of endothelial cells by bFGF. Collagenese activities in the renal tissues irrespetive of malignancy were quite low in our assay system using by Collageno kit CLN-100.These data suggest that bFGF activity may acularate growth and proliferation of RCC at least in VHL disease.

Von Hippel-Lindau（VHL）病表现为小脑血管母细胞瘤、视网膜血管瘤以及胰腺、肾脏和附睾的囊肿，众所周知其与肾细胞癌（RCC）高度相关。散发性肾细胞癌也是一种高度血管化的肿瘤。这些临床证据提示肾细胞癌的生长增殖与肿瘤血管生成密切相关。本文对12例肾细胞癌（10例散发，2例VHL病）及其相应的自体正常肾组织中碱性成纤维细胞生长因子（bFGF）活性进行了测定和比较。散发性肾细胞癌和正常肾组织中bFGFs分别为98.2 × 38.68和143.2 × 31.16 fmol/mg。蛋白质（平均值 *SD，n=10）。恶性肿瘤组织中bFGF活性明显低于相应的自体正常组织。2例VHL患者肾细胞癌和非癌肾组织bFGF活性分别为137、632和82、44 fmol/mg。通常，bFGF作为惰性形式存在于细胞外基质中。胶原酶活性可能在bFGF破坏细胞外基质和动员内皮细胞方面具有重要作用。在我们的检测系统中，用CLN-100型胶原试剂盒检测的肾组织中的胶原活性很低，提示bFGF活性可能促进肾细胞癌的生长和增殖，至少在VHL病中是如此。